Human gamma-herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV) are associated with a variety of cancers. Vaccines against EBV and KSHV would reduce the occurrence of virus-associated cancers. Major challenges to vaccine development for herpesviruses include the immunologically silent nature of latency and the large collections of immune evasion genes encoded by the viruses. Our goal is to understand the interactions between the virus and the host immune response. The knowledge will be utilized to develop new vaccine strategies. This Program will focus the research on KSHV. However, KSHV does not have robust lytic replication or a small animal infection model. To complement the studies in KSHV, this Program will also exploit an experimental model based on a closely related rodent virus, murine gammaherpesvirus 68 (MHV-68, also known as yHV-68, or MuHV-4), for proof of principle experiments. All of the research projects in this Program will investigate the effects of cellular factors on various aspects of viral replication and viral immune evasion mechanisms. Thus, it will be more efficient to organize a core that can provide a centralized, coordinated, and cost-efficient service which includes providing assays, reagents, and expertise on KSHV and MHV-68. Core B will generate and provide recombinant KSHV and MHV-68 viruses. In addition, the Core will provide in vitro cell culture systems and the virological assays with protocols, reagents and controls.